Treatment of fibromyalgia with ubiquinone 10 and succinic acid

ABSTRACT

A method is described for using a combination of ubiquinone 10 and succinic acid in the treatment of human patients afflicted with fibromyalgia to alleviate one or more symptoms associated with that disease state. Fibromyalgia positive patients treated buccally, sublingually or by oral ingestion administration of ubiquinone 10 and succinic acid enjoy a reduction in clinical symptoms of the disease.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority under 35 U.S.C. §119(e) to U.S.Provisional Application No. 60/181,314, filed Feb. 9, 2000, which isexpressly incorporated by reference herein.

FIELD OF INVENTION

[0002] The present invention relates to a composition and method fortreatment of patients afflicted with fibromyalgia. More particularly,this invention is directed to a composition and method for relievingsymptoms associated with fibromyalgia in human patients by administeringa combination of ubiquinone 10 and succinic acid.

BACKGROUND AND SUMMARY OF THE INVENTION

[0003] Fibromyalgia is a common disabling disorder characterized bychronic musculoskeletal aches and pain, stiffness, general fatigue, andsleep abnormalities including diminished stage four sleep. Examinationof affected patients reveals increased tenderness at muscle and tendoninsertion sites, known as “tender points.” Fibromyalgia patientsexperience severe morning stiffness and a generalized decreased ofoverall physical function, and they are often prone to headaches, memoryand concentration problems, dizziness, numbness and tingling, and crampyabdominal or pelvic pain. Fibromyalgia affects 2-4% of the populationand is most frequently found in women between 20 and 50 years old,although it can also affect men, the elderly and minors.

[0004] Diagnosis of fibromyalgia is often overlooked due to the generalnature of the symptoms and the lack of diagnostic lab or x-rayabnormalities. The disorder is often concomitant with, masked by orconfused with other diseases such as rheumatoid arthritis, chronicfatigue syndrome or irritable bowl syndrome. However, chronic fatiguesyndrome (CFS) can be distinguished from fibromyalgia because patientswith CFS are likely to have symptoms of viral illnesses such as fever,sore throat, and lymph node pain. A physician can positively diagnosefibromyalgia syndrome by finding the symptoms of musculoskeletal painthroughout the body and pain at more than 11 of 18 symmetricallydistributed characteristic “tender points” when a finger pressure ofabout 4 kg is applied to the area, which test is known as the “tenderpoint index,” or when tender points are detected with dolorimetry.

[0005] Currently the best treatment available for fibromyalgia consistsof a combination of analgesics, sleep aids, exercise programsemphasizing stretching and cardiovascular fitness, relaxation techniquesand other measures to reduce muscle tension, and educational programs toreduce emotional and physical stress. Numerous pharmaceutical regimenshave been tried including treatment with serotonin modulators andantisera to endogenous psychoactive agents. Therapeutic response can beassessed by the reduction of pain in the tender point index andimprovement in several generalized criteria such as physical function,stiffness, fatigue, depression, tenseness, etc. Responses to thesevarious therapies have proven variable within a patient pool and haverarely exceeded modest relief of some symptoms. Often, initialtherapeutic gains are temporary with the long term outcome marginally ifat all distinguishable from placebo results.

[0006] Ubiquinone 10 and succinic acid are physiological substancespresent in all living cells. Succinic acid is oxidized to fumarate asone of the nine steps in the citric acid cycle, and oxidation ofsuccinic acid results in the release of two electrons which aretransferred to flavin adenine dinucleotide (FAD) to generate the reducedform of the molecule, FADH₂. Electrons are then sequentially transferredbetween various flavin-linked dehydrogenases in the electron transportpathway localized on the inner mitochondrial membrane. Electrontransport results in proton transport across the mitochondrial membraneand powers ATP synthesis through coupling with the oxidativephosphorylation pathway.

[0007] Ubiquinone 10 (CoQ10) is a lipophilic electron carrier thattransports electrons between the various flavin-linked dehydrogenases inthe electron transport pathway through reduction and oxidation of CoQ10.CoQ10 contains ten isoprene units in the multiprenyl side chain of themolecule which renders CoQ10 lipophilic and facilitates interaction ofthe molecule with the inner mitochondrial membrane where the componentsof the electron transfer chain are located. CoQ10 complexes withsuccinic acid and succinate dehydrogenase, the enzyme responsible forcatalyzing the oxidation of succinic acid to fumarate, and acts as anelectron carrier to facilitate the transfer of electrons from succinicacid to FAD. CoQ10 is widely distributed in tissues and may also act anantioxidant for such endogenous molecules as low density lipoproteins.

[0008] There exists a significant need for more effective therapy forpatients afflicted with fibromyalgia. The present invention is directedto a method for treating a human patient suffering from fibromyalgia toproduce a therapeutic response in the patient. The method comprises thestep of administering to the patient ubiquinone 10 and succinic acideach at a dose of about 5 to about 500 mg/70 kg patient. In oneembodiment of the invention the ubiquinone 10 and the succinic acid areeach administered at a dose of about 50 to about 400 mg/70 kg patientand are administered by oral ingestion, bucally, sublingually, orparenterally. In another embodiment of the invention the ubiquinone 10and succinic acid are each administered at a dose of about 50 to about200 mg/70 kg patient. The ubiquinone 10 and succinic acid may beadministered in a solid, liquid, or saliva-soluble dosage form, such asa lozenge. The daily doses can be divided into multiple dosesadministered one or more times per day.

[0009] In another embodiment, the invention provides a pharmaceuticalcomposition comprising therapeutically effective amounts of ubiquinone10 and succinic acid as the active ingredients, and a pharmaceuticallyacceptable carrier therefor. The pharmaceutical composition can be inthe form of a liquid solution, a capsule, a caplet, a tablet, agel-seal, or a lozenge and can be adapted for oral or parenteraladministration.

DETAILED DESCRIPTION OF THE INVENTION

[0010] The present invention provides a method for treating a humanpatient suffering from fibromyalgia to produce a therapeutic response inthe patient. The method comprises the step of administering to thepatient ubiquinone 10 and succinic acid each at a dose of about 5 toabout 500 mg/70 kg patient. The ubiquinone 10 and succinic acid may beadministered by oral ingestion, bucally, sublingually, or parenterallyand may be administered in a pharmaceutically acceptable solid, liquid,or saliva-soluble dosage form, such as a lozenge. In a preferredembodiment, the ubiquinone 10 and succinic acid are taken with food. Inaccordance with the present invention, there is also provided apharmaceutical composition comprising therapeutically effective amountsof ubiquinone 10 and succinic acid as the active ingredients, and apharmaceutically acceptable carrier therefor. The pharmaceuticalcomposition may be in the form of a suspension, a capsule or caplet, atablet, a gel-seal, or a lozenge, and may be adapted for oral orparenteral administration.

[0011] Succinic acid is an intermediate in the citric acid cycle and,thus, is a physiological compound found in living cells. Succinic acidis oxidized to form fumarate as a step in the citric acid cycle and,upon oxidation of succinic acid, two electrons are released and aretransferred to FAD to generate the reduced form of the molecule, FADH₂,as the first step in the electron transport pathway. Electrons are thensequentially transferred between various flavin-linked dehydrogenases inthe electron transport pathway resulting in the generation of ATPthrough coupling with oxidative phosphorylation. Ubiquinone 10 is anelectron carrier that facilitates transport of electrons between thevarious flavin-linked dehydrogenases in the electron transport pathway,and complexes with succinic acid and succinate dehydrogenase tofacilitate the transfer of electrons generated by oxidation of succinicacid to FAD. Methods of producing ubiquinone 10 are well known in theart and one such method is disclosed in U.S. Pat. No. 4,070,244incorporated herein by reference in its entirety. Succinic acid iscommercially available from Aldrich Chemical Company, Milwaukee, Wis.

[0012] In accordance with the present invention, a method is providedfor treating a human patient suffering from fibromyalgia to produce atherapeutic response. A “therapeutic response” is a response totreatment with ubiquinone 10 and succinic acid in which one or more ofthe clinical symptoms of fibromyalgia in a patient with the disease areprevented, reduced, or stabilized whether such improved patientcondition is permanent or temporary. Ubiquinone 10 and succinic acid mayalso be used in combination for the treatment of other disease statesincluding such diseases as adult onset diabetes, autoimmune disorderssuch as lupus erythematosus, and chronic fatigue syndrome. A“therapeutic response” to treatment with ubiquinone 10 and succinic acidfor any of these disease states is also a response in which one or moreof the clinical symptoms of disease are prevented, reduced, orstabilized whether such improved patient condition is permanent ortemporary. The term “succinic acid” as used herein to claim and describethe method and composition of the present invention will be understoodto include pharmaceutically acceptable salts of succinic acid, succinicacid anhydride and succinic acid esters which, upon administration to apatient, can serve as a source of succiniate in vivo via in vivohydrolysis or neutralization under physiological conditions.

[0013] In one embodiment of this invention, the method for treating apatient suffering from fibromyalgia to produce a therapeutic responsecomprises the step of administering ubiquinone 10 and succinic acid byoral ingestion each at a dose of about 5 to about 500 mg/70 kg patient.In another embodiment, the compounds are administered at a dose of about50 to about 400 mg/70 kg patient. In an alternate embodiment, thecompounds are administered at a dose of about 50 to about 200 mg/70 kgpatient for relief of one or more symptoms of fibromyalgia. The dailydoses of ubiquinone 10 and succinic acid can be administered as singledaily doses or in more than one dose per day until the patient'ssymptoms of fibromyalgia have subsided. The ubiquinone 10 and succinicacid may also be administered in different weight ratios in single dailydoses or in a multi-dose regimen, and, preferably, are taken with food.In a preferred embodiment, for example, the ubiquinone 10 isadministered with food at about 100 mg/70 kg patient per dose and thesuccinic acid at about 400 mg/70 kg patient per dose in single or in twodaily doses. In another preferred embodiment, the ubiquinone 10 isadministered at about 25 mg/70 kg patient per dose and the succinic acidat about 100 mg per dose and the compounds are taken with food 2-4 timesdaily with food to achieve daily ubiquinone 10 and succinic acid dosesof 50-100 mg/70 kg patient and 200-400 mg/70 kg patient, respectively.In yet another preferred embodiment these same ubiquinone 10 andsuccinic acid doses are administered twice daily with food to achievedaily doses of 50 and 200 mg/70 kg patient, respectively.

[0014] Oral ingestion may be achieved by the use of such dosage forms ofubiquinone 10 and succinic acid as syrups, sprays, or other liquiddosage forms, a gel-seal, or a capsule or caplet. Buccal and sublingualadministration comprises contacting the oral and pharyngeal mucosa ofthe patient with the dose of ubiquinone 10 and succinic acid either in apharmaceutically acceptable liquid dosage form, such as a syrup or aspray, or in a saliva-soluble dosage form which is held in the patient'smouth to form a saliva solution of ubiquinone 10 and succinic acid incontact with the oral and pharyngeal mucosa. Exemplary of saliva-solubledosage forms are lozenges, tablets, and the like. Parenteraladministration can be accomplished by injection of a liquid dosage formof ubiquinone 10 and succinic acid, such as by injection of a solutionof the two compounds dissolved in a pharmaceutically acceptable buffer.Such parenteral administration may be intradermal, subcutaneous,intramuscular, intraperitoneal, or intravenous.

[0015] The ubiquinone 10 and succinic acid intended for buccal orsublingual administration in accordance with the present invention isadministered to the patient in a dosage form adapted to promote contactof the administered ubiquinone 10 and succinic acid with the patient'soral and pharyngeal mucosa. Thus, the dosage form can be in the form ofa liquid solution such as a syrup, spray, or other liquid dosage form tobe administered and used by the patient in a manner which promotescontact of the ubiquinone 10 and succinic acid components with oralmucosal tissues, for example, by holding the ubiquinone 10 and succinicacid solution in the mouth for up to one or two minutes. Alternatively,the ubiquinone 10 and succinic acid can be administered by oralingestion wherein the compounds are formulated into a syrup to beswallowed by the patient and not held in the mouth. Syrups for eitheruse may be flavored or unflavored and may be formulated using a bufferedaqueous solution of ubiquinone 10 and succinic acid as a base with addedcaloric or non-caloric sweeteners, flavor oils and pharmaceuticallyacceptable surfactant/dispersants. Other liquid dosage forms, includingsolutions or sprays containing ubiquinone 10 and succinic acid, can beprepared in a similar manner and can be administered buccally,sublingually, or by oral ingestion.

[0016] Preferably, the ubiquinone 10 and succinic acid forbuccal/sublingual administration in the present invention is formulatedinto a solid dosage form, such as a lozenge or a tablet. Thisformulation preferably contains ubiquinone 10, succinic acid and asaliva-soluble carrier and may optionally contain desirable excipients,such as buffers, or tableting aids. The solid dosage form is formulatedto dissolve, when held in a patient's mouth, to form a saliva solutionof the ubiquinone 10 and succinic acid to promote contact of thecompounds with the oral and pharyngeal mucosa.

[0017] In one embodiment, the solid dosage form is in the form of alozenge adapted to be dissolved upon contact with saliva in the mouth,with or without the assistance of chewing, to form a saliva solution ofubiquinone and succinic acid. In this embodiment, lozenges areformulated to provide about 5 to about 500 mg/70 kg patient ofubiquinone 10 and succinic acid, preferably about 50 to about 400 mg/70kg patient. In another preferred embodiment, about 50 to about 200 mg/70kg patient of ubiquinone 10 and succinic acid is provided upondissolution of the dosage form in saliva in the mouth. Ubiquinone 10 andsuccinic acid are preferably taken with food.

[0018] Lozenges for use in accordance with this invention can beprepared, for example, by art-recognized techniques for formingcompressed tablets where the ubiquinone 10 and succinic acid isdispersed on a compressible solid carrier, optionally combined with anyappropriate tableting aids such as a lubricant (e.g.,magnesium-stearate) and is compressed into tablets. The solid carriercomponent for such tableting formulations can be a saliva-soluble solid,such as a cold water-soluble starch or a monosaccharide or disaccharide,so that the lozenge will readily dissolve in the mouth to release thecontained ubiquinone 10 and succinic acid in saliva solution for contactwith and absorption by the oral/pharyngeal mucosa when the lozenge isheld in the mouth. The pH of the above-described formulations can rangefrom about 4 to about 8.5. Lozenges for use in accordance with thepresent invention can also be prepared utilizing other art-recognizedsolid unitary dosage formulation techniques.

[0019] Tablets for use in accordance with this invention can be preparedin a manner similar to that described for preparation of lozenges or byother art-recognized techniques for forming compressed tablets such aschewable vitamins. Suitable solid carrier components for tabletinginclude manitol, microcrystalline cellulose, carboxymethyl cellulose,and dibasic calcium phosphate.

[0020] Solid dosage forms for oral ingestion administration include suchdosage forms as caplets, capsules, and gel-seals. Such solid dosageforms can be prepared using standard tableting protocols and excipientsto provide ubiquinone 10 and succinic acid-containing capsules, caplets,or gel-seals. Any of the solid dosage forms for use in accordance withthe invention, including lozenges and tablets, may be in a form adaptedfor sustained release of the ubiquinone 10 and succinic acid.

[0021] In accordance with one embodiment of the present invention apharmaceutical composition is provided comprising therapeuticallyeffective amounts of ubiquinone 10 and succinic acid, and apharmaceutically acceptable carrier therefor. “Therapeutically effectiveamounts” of ubiquinone 10 and succinic acid are amounts of the compoundswhich prevent, reduce, or stabilize one or more of the clinical symptomsof fibromyalgia in a patient suffering from the disease whether suchimproved patient condition is permanent or temporary. In one embodimentthe pharmaceutical composition comprises about 5 to about 500 mg/70 kgpatient of ubiquinone 10 and succinic acid per dose in combination witha pharmaceutically acceptable carrier. A preferred pharmaceuticalcomposition comprises about 50 to about 400 mg/70 kg patient per dose ofeach of the two compounds in combination with the carrier. In anotherpreferred embodiment, the pharmaceutical composition comprises about 50to about 200 mg/70 kg patient of ubiquinone 10 and succinic acid perdose in combination with the pharmaceutically acceptable carrier. Theubiquinone 10 and succinic acid may be present in the pharmaceuticalcomposition at different weight ratios. Most preferably, thepharmaceutical composition comprises about 100 mg/70 kg patient per doseof ubiquinone 10 and 400 mg/70 kg patient per dose of succinic acid. Inanother preferred embodiment, the pharmaceutical comprises about 25mg/70 kg patient per dose of ubiquinone 10 and 100 mg per dose ofsuccinic acid administered 2-4 times daily with food to achieve dailyubiquinone 10 and succinic acid doses of 50-100 mg/70 kg patient and200-400 mg/70 kg patient, respectively. In yet another preferredembodiment the pharmaceutical composition comprises about 50 mg/70 kgpatient per dose of ubiquinone 10 and 200 mg/70 kg patient per dose ofsuccinic acid administered twice daily with food to achieve daily dosesof 100 and 400 mg/70 kg patient, respectively.

[0022] A “pharmaceutical acceptable carrier” for use in accordance withthe invention is compatible with other reagents in the pharmaceuticalcomposition and is not deleterious to the patient. The pharmaceuticallyacceptable carrier formulations for pharmaceutical compositions adaptedfor oral ingestion or buccal/sublingual administration includinglozenges, tablets, capsules, caplets, gel-seals, and liquid dosageforms, including syrups, sprays, and other liquid dosage forms, havebeen described above. Ubiquinone 10 and succinic acid can also beadapted for parenteral administration in accordance with this inventionusing a pharmaceutical acceptable carrier adapted for use in a liquiddose form. Thus, ubiquinone 10 and succinic acid can be administereddissolved in a buffered aqueous solution typically containing astabilizing amount (1-5% by weight) of albumin or blood serum. Such aliquid solution of ubiquinone 10 and succinic acid may be in the form ofa clarified solution or a suspension. Exemplary of a buffered solutionsuitable as a carrier of ubiquinone 10 and succinic acid administeredparenterally in accordance with this invention is phosphate bufferedsaline prepared as follows:

[0023] A concentrated (20×) solution of phosphate buffered saline (PBS)is prepared by dissolving the following reagents in sufficient water tomake 1,000 ml of solution: sodium chloride, 160 grams; potassiumchloride, 4.0 grams; sodium hydrogen phosphate, 23 grams; potassiumdihydrogen phosphate, 4.0 grams; and optionally phenol red powder, 0.4grams. The solution is sterilized by autoclaving at 15 pounds ofpressure for 15 minutes and is then diluted with additional water to asingle strength concentration prior to use.

[0024] The daily doses of ubiquinone 10 and succinic acid foradministration in accordance with this invention can be administered assingle doses, or they can be divided and administered as a multiple-dosedaily regimen. Thus, the doses of ubiquinone 10 and succinic acid may beadministered 1 to 4 times a day until patient symptoms of fibromyalgiahave subsided or are stabilized. Further, a staggered regimen, forexample, one to three days of buccal/sublingual ubiquinone 10 andsuccinic acid treatments per week, can be used as an alternative todaily treatment, and for the purpose of defining this invention suchintermittent or staggered daily regimen is considered to be equivalentto every day treatment and within the scope of this invention.

EXAMPLE 1 Preparation Of Ubiquinone 10 And Succinic Acid-ContainingLiquid Solutions

[0025] Ubiquinone 10 is synthesized according to the procedure describedin U.S. Pat. No. 4,070,244 incorporated herein by reference in itsentirety. Succinic acid is purchased from Aldrich Chemical Company,Milwaukee, Wis. A ubiquinone 10 and succinic acid-containing liquidsolution is prepared by first dissolving ubiquinone 10 and succinic acidin phosphate-buffered saline. To prepare a physiologicalphosphate-buffered saline solution for dissolution of the ubiquinone 10and succinic acid, a concentrated (20×) solution of phosphate bufferedsaline (PBS) is diluted to obtain a 1×solution. The 20×PBS solution isprepared by dissolving the following reagents in sufficient water tomake 1,000 ml of solution: sodium chloride, 160 grams; potassiumchloride, 4.0 grams; sodium hydrogen phosphate, 23 grams; potassiumdihydrogen phosphate, 4.0 grams; and optionally phenol red powder, 0.4grams. The PBS solution is then sterilized by autoclaving at 15 poundsof pressure for 15 minutes and is diluted with additional sterile waterto a 1×concentration prior to dissolution of the ubiqunone 10 andsuccinic acid. To prepare a dose form for intravenous administration,ubiquinone 10 and succinic acid are dissolved in 1×PBS at concentrationsof 0.5 and 2 mg/ml, respectively, and the resulting solution (200 ml) isdispensed into sealable translucent plastic bags for use in intravenousadminstration of the compounds. These steps are performed under sterileconditions. Alternatively, ubiquinone 10 and succinic acid are dissolvedin sterile 1×PBS at concentrations of 100 and 400 mg/ml, respectively,and 10 ml aliquots are dispensed, under sterile conditions, into glassvials which are then sealed with a rubber septum. Such dosage forms areuseful for parenteral administration of the compounds by subcutaneous,intramuscular, intraperitoneal, and intradermal injection atapproximately 1 ml per dose. The buffered aqueous solution of ubiquinone10 and succinic acid is also used as a base for preparing other liquidformulations of the compounds. For example, a syrup is prepared byadding art-recognized caloric or non-caloric sweetners, flavor oils, andpharmaceutically acceptable surfactants/dispersants to an aqueoussolution of ubiquone 10 and succinic acid. Such a syrup dosage formcontains ubiquinone 10 and succinic acid at concentrations of 100 and400 mg/ml, respectively, and is administered in 1 ml amounts. Aubiquinone 10 and succinic acid-containing spray is similarlyformulated, but contains flavoring in an aqueous form, and a convenientmeans of delivering an aerosol spray is utilized.

EXAMPLE 2 Preparation of Ubiquinone 10 And Succinic Acid-ContainingLozenges

[0026] Lozenges for use in accordance with this invention can beprepared by art-recognized techniques for forming compressed tablets.The ubiquinone 10 and succinic acid is dispersed on a compressible solidcarrier and is formed into tablets each containing a predeterminedamount of the active ingredients. For example, each lozenge may contain100 mg of ubiquinone 10 and 400 mg of succininc acid, or, alternatively,25 mg of ubiquinone 10 and 100 mg of succinic acid or any othertherapeutically effective amounts. The solid carrier component for suchtableting formulations can be a saliva-soluble solid, such as a coldwater-soluble starch or a monosaccharide or disaccharide, so that thelozenge will readily dissolve in the mouth to release the containedubiquinone 10 and succinic acid in saliva solution for contact with andabsorption by the oral/pharyngeal mucosa when the lozenge is held in themouth. A preferred solid carrier is dibasic calcium phosphate. Theubiquinone 10 and succinic acid is also optionally combined with anyappropriate tableting aids such as a lubricant (e.g.,magnesium-stearate), a binding agent, a wetting agent, or adisintegrant. The product is then shaped by art-recoginized techniquesinto the desired delivery form. The pH of the formulations ranges fromabout 4 to about 8.5.

EXAMPLE 3 Preparation of Ubuquinone 10 And Succinic Acid-ContainingTablets

[0027] Tablets for use in accordance with this invention can be preparedin a manner similar to that described in Example 2 for preparation oflozenges except that a saliva-soluble solid carrier for dissolution inthe mouth is not required. The ubiquinone 10 and succinic acid may bepresented as a powder, and suitable solid carrier components fortableting include manitol, microcrystalline cellulose, and carboxymethylcellulose. A preferred solid carrier for use in accordance with theinvention is dibasic calcium phosphate. Tablets may also be prepared byother art-recognized techniques for forming compressed tablets such aschewable vitamins.

EXAMPLE 4 Treatment Of A Female Fibromyalgia Subject With Ubiquinone 10And Succinic Acid Using A Single Daily Dose Regimen

[0028] A 45 year old female subject presents with fatigue, dizziness,muscle cramps and pain, joint pain, headaches, and diminished sleep. Thesubject is examined, and is diagnosed as suffering from fibromyalgia byfinding pain at 14 of 18 characteristic tender points when a fingerpressure of about 4 kg is applied to the area. The subject is treatedwith ubiquinone 10 and succinic acid-containing lozenges by buccaladministration, with each lozenge containing 25 mg of ubiquinone 10 and100 mg of succinic acid, in four daily doses with food for one month.After 1 month of daily treatment with the ubiquinone 10 and succinicacid-containing lozenges, the subject's condition is improved with thedizziness, muscle and joint pain, and headaches diminished. Considerableimprovement in physical activity and sleep is also observed. The subjectis reexamined to determine the tender point index after treatment withubiquinone 10 and succinic acid and pain is found at only 4 of the 18characteristic tender points. The subject continues on the sametreatment regimen and no side effects are observed.

EXAMPLE 5 Treatment of a Male Fibromyalgia Subject With Ubiquinone 10And Succinic Acid

[0029] A 37 year old male subject presents with general fatigue,restlessness, muscle and joint pain, numbness, and abdominal cramps. Thesubject is examined, and is positively diagnosed as suffering fromfibromyalgia by finding pain at 17 of 18 characteristic tender pointswhen 4 kg of finger pressure is applied. The subject is treated withubiquinone 10 and succinic acid by parenteral administration of aubiquinone 10 and succinic acid-containing buffered liquid solution. Theliquid dose formulation is administered so that the subject receives adose of 100 mg per day of ubiquinone 10 and 400 mg per day of succinicacid with food for 14 days. The subject is reexamined to determine thesubject's tender point index after 14 days and pain is found at only 6of the 18 characteristic tender points. Considerable improvement in thesubject's muscle and joint pain and abdominal pain are observed and thesubject indicates that he feels better physically and mentally. Thesubject continues treatment on the same treatment regimen as describedin Example 4 and his symptoms continue to subside. The subject does notcomplain of any side effects.

EXAMPLE 6 Treatment of a Female Fibrobyalgia Subject With Ubiquinone 10And Succinic Acid Using A Multi-Dose Daily Regimen

[0030] A 29 year old female subject presents with muscle cramps, jointpain, stiffness, and general fatigue. The subject also complains ofsleep abnormalities. The subject is examined, and is positivelydiagnosed as suffering from fibromyalgia by finding pain at 15 of 18characteristic tender points when 4 kg of finger pressure is applied tothe area. The subject is treated with ubiquinone 10 and succinic acid byoral ingestion of a ubiquinone 10 and succinic-containing syrup whereinthe subject swallows the syrup upon administration and does not hold thesyrup in the mouth for a period of time before swallowing. Each dose ofthis liquid formulation contains 25 mg of ubiquinone 10 and 100 mg ofsuccinic acid, and is administered in 4 daily doses with food for aperiod of 3 weeks. The subject is reexamined after 3 weeks and pain isfound at only 2 of the 18 characteristic tender points. Considerableimprovement in the subject's muscle and joint pain are observed and thesubject indicates that she feels better physically. The subjectcontinues on the same treatment regimen and does not complain of anyside effects.

EXAMPLE 7 Treatment of a Female Fibromyalgia Subject With Ubiquinone 10And Succinic Acid

[0031] A 48 year old female was positively diagnosed with fibromyalgia.The subject found no relief for her pain after receiving standardmedical treatment. The subject began treatment with 50 mg of ubiquinone10 and 200 mg of succinic acid in capsule form twice daily with food.The subject experienced dramatic relief of her symptoms by the fifth dayafter treatment commenced with almost complete cessation of symptoms bythe fourteenth day after treatment began. She improved further over asix week period until she became asymptomatic, and continues on the sametreatment regimen.

EXAMPLE 8 Treatment of a Female Fibromyalgia Subject With Ubiquinone 10And Succinic Acid

[0032] A 40 year old female was diagnosed with fibromyalgia and begantreatment with 100 mg of ubiquinone 10 and 400 mg of succinic acid in asingle daily dose in capsule form with food. The subject experiencedsome stomach upset with 400 mg of succinic and her succinic acid dosewas reduced to 200 mg per day. The subject experienced dramatic relieffrom her pain and other symptoms and became asymptomatic within 30 days.She continues on the same treatment regimen with no recurrence ofsymptoms.

EXAMPLE 9 Treatment Of a Female Fibromyalgia Subject With Ubiquionone 10And Succinic Acid

[0033] A 32 year old patient was diagnosed with fibromyalgia and begantreatment with ubiquinone 10 and succinic acid three months later. Thesubject was treated with 100 mg of ubiqinone 10 and 200 mg of succinicacid twice daily in capsule form with food. The subject noted somerelief from her symptoms by the end of the first week of treatment. Shecontinued to improve and complete cessation of symptoms was observed bythe end of thirty days. She continues on the same treatment regimen andhas no reoccurence of symptoms.

EXAMPLE 10 Treatment of a Female Lupus Erythematosus Subject WithUbiquinone 10 And Succinic Acid

[0034] A 60 year old female diagnosed with lupus found no satisfactoryresults with standard medical treatment. The subject began treatmentwith 100 mg of ubiquinone 10 and 400 mg of succinic acid in capsule formwith food in two daily doses. The subject experienced remission of hersymptoms within about two weeks after treatment began and continues onthe same treatment regimen.

EXAMPLE 11 Treatment of a Female Lupus Erythematosus Subject WithUbiquinone 10 And Succinic Acid

[0035] A 65 year old female was diagnosed with lupus erythematosus andwas treated using the same regimen as described in Example 10. Thesubject experienced complete remission of symptoms in about 2 weeks, andcontinues on the same treatment regimen.

EXAMPLE 12 Treatment of a Female Subject With Chronic Fatigue SyndromeWith Ubiquinone 10 And Succinic Acid

[0036] A 40 year old female subject was diagnosed with chronic fatiguesyndrome and was sent to numerous specialists without improvement. Thesubject began treatment with 100 mg of ubiquinone 10 and 400 mg ofsuccinic acid in capsule form with food once daily. The subject'ssymptoms subsided within 3 days and she was asymptomatic within twoweeks, and continues on the same treatment regimen without recurrence ofsymptoms.

EXAMPLE 13 Treatment of a Male Diabetes Subject With Ubiquinone 10 AndSuccinic Acid

[0037] A 62 year old male subject was diagnosed with diabetes and hadhigh blood sugar levels even with medical treatment. The subject begantreatment with 50 mg of ubiquinone 10 and 200 mg of succinic acid incapsule form twice daily with food. The subject's blood sugar level waslowered to 112 and has been maintained at that level since theubiquinone 10 and succinic acid treatment was initiated. The subjectcontinues on the same treatment regimen.

EXAMPLE 14 Treatment Of A Male Diabetes Subject With Ubiquinone 10 AndSuccinic Acid

[0038] A 60 year old male subject was diagnosed with diabetes and hadhigh blood sugar levels even with medical treatment. The subject begantreatment with 50 mg of ubiquinone 10 and 200 mg of succinic acid incapsule form twice daily with food. The subject's blood sugar level waslowered and swelling in his feet subsided. The subject continues on thesame treatment regimen.

EXAMPLE 15 Treatment of a Male Diabetes Subject With Ubiquinone 10 AndSuccinic Acid

[0039] A 70 year old male subject was diagnosed with diabetes. He begantreatment with 100 mg of ubiquinone 10 and 400 mg of succinic acid withfood in a single daily dose in capsule form. The treatment withubiquinone 10 and succinic acid has lowered and controlled the subject'sblood glucose level and he continues on the same treatment regimen.

What is claimed is:
 1. A method for treating a human patient sufferingfrom fibromyalgia to produce a therapeutic response in said patient,said method comprising the step of administering to the patientubiquinone 10 and succinic acid each at a dose of about 5 to about 500mg/70 kg patient.
 2. The method of claim 1 wherein the ubiquinone 10 andthe succinic acid are each administered at a dose of about 50 to about400 mg/70 kg patient.
 3. The method of claim 1 wherein the ubiquinone 10and the succinic acid are each administered at a dose of about 50 toabout 200 mg/70 kg patient.
 4. The method of claim 1 wherein theubiquinone 10 and the succinic acid are formulated in combination in apharmaceutically acceptable solid dosage form.
 5. The method of claim 1wherein the ubiquinone 10 and the succinic acid are formulated incombination in a pharmaceutically acceptable liquid dosage form.
 6. Themethod of claim 4 wherein the solid dosage form is a saliva-solublesolid dosage form of said combination which is administered by beingintroduced into the mouth of the patient and held in the mouth for aperiod of time sufficient to dissolve in saliva in the patient's mouthto form a saliva solution comprising ubiquinone 10 and succinic acid. 7.The method of claim 6 wherein the solid dosage form is a lozenge.
 8. Themethod of claim 1 wherein the ubiquinone 10 and the succinic acid areadministered by oral ingestion.
 9. The method of claim 1 wherein theubiquinone 10 and the succinic acid are administered bucally.
 10. Themethod of claim 1 wherein the ubiquinone 10 and the succinic acid areadministered sublingually.
 11. The method of claim 1 wherein theubiquinone 10 and the succinic acid are administered parenterally. 12.The method of claim 1 wherein the dose of ubiquinone 10 and succinicacid is administered 1 to 4 times a day until the patient's symptoms offibromyalgia have subsided.
 13. A pharmaceutical composition comprisingtherapeutically effective amounts of ubiquinone 10 and succinic acid asthe active ingredients, and a pharmaceutically acceptable carriertherefor.
 14. The pharmaceutical composition of claim 13 in the form ofa liquid solution.
 15. The pharmaceutical composition of claim 13 in theform of a capsule or caplet.
 16. The pharmaceutical composition of claim13 in the form of a tablet.
 17. The pharmaceutical composition of claim13 in gel-seal form.
 18. The pharmaceutical composition of claim 13 inthe form of a lozenge.
 19. The pharmaceutical composition of claim 13adapted for oral administration.
 20. The pharmaceutical composition ofclaim 13 adapted for parenteral administration.